The goal of this proposal is to assess glycated CD59 in human serum as a pathogenically relevant early bio-marker for screening of gestational diabetes mellitus (GDM). This proposal is highly translational and addresses major Public Health priorities because 1) diabetes affects H 25 million Americans, 2) and GDM is a major source of adverse pregnancy outcomes including macrosomia and pre-eclampsia. The proposed work opens the possibility of using glyCD59 as a biomarker for GDM, an innovative departure from the use of OGTT, a cumbersome, costly and time-consuming test with poor reproducibility and many times unwanted effects including nausea and vomiting. A simpler, easy to use, patient friendly marker that is also involved in the pathogenesis of diabetes and its complications may help fulfill an important clinical need in the widespread screening for GDM and prevention of associated adverse outcomes. The applicants have 1) discovered that human CD59 is inactivated by glycation, 2) provided evidence for a link between the complement system and the pathogenesis of the complications of diabetes, and 3) developed key reagents that allow quantification of glycated hCD59 in human fluids and tissues. Specifically, we have demonstrated that 1) glycated CD59 is present in target organs of diabetic complications, and 2) glyCD59 can be readily measured in normal urine and serum. Furthermore, our preliminary data show that glyCD59 is a) significantly increased (3-4 fold) in the serum of diabetic and pre-diabetics individuals, and b) seems to respond faster than HbA1c to changes in glycemic load within an individual All necessary tools and expertise to accomplish our aim are available in the laboratory of the applicant and expert collaborators, including monoclonal antibodies specific for glycated CD59 and assay calibrators, access to large and diverse population of pregnant women undergoing pre-natal care at BWH, and diagnostic tools, equipment and expertise to necessary to conduct all studies proposed in the application. Successful accomplishment of our aims would represent a major advancement in screening and early diagnosis of GDM.